Introduction and summary

Rett syndrome is a developmental disorder of the central nervous system (brain and cranial nerves) with metabolic components.
A metabolic disease or metabolic disorder is a hereditary condition in which substances in the cells of the body are processed less well.

As a result, a certain substance or waste product can accumulate and lead to complaints.

 

Rett syndrome occurs almost exclusively in girls. Girls have a deficiency of hereditary material from the MECP2 gene. A change occurs in the MECP2 gene (gene mutation) on the X chromosome.
Children with Rett syndrome develop normally in the first few months, but from about 6 to 18 months, sometimes 24 months, the symptoms begin. These include loss of use of hands, typical hand movements such as wringing or clapping, other motor skills (also consider dyspraxia, very difficult to control all body movements (ataxia), including eye movements), speech, cognitive skills and difficulty with communication. Epilepsy and breathing problems can also occur.

 

Other names for Rett syndrome are the abbreviations RTT or RTS.

 

The development of the child

Before birth
Before birth, there is a deficiency of a specific protein in the brain development of people with this condition. This is the protein methyl-CpG binding protein-2, also abbreviated as MECP2. This deficiency is caused by an error on a chromosome.
The brain cells contain fewer extensions with which they can communicate with other brain cells. These extensions are also too short.
The image below shows the normal length and amount of extensions of a brain cell.

 

 

After birth to 18 to 24 months

At birth, a baby is often limp, due to low muscle tone. This often goes unnoticed.
The child's development initially proceeds without problems, then stops at about half a year to one and a half years, sometimes at 24 months, and can then deteriorate. No new skills are learned. Sometimes the deterioration is slow, sometimes very fast.

The children cry a lot during this phase and even seem inconsolable. The crying fits can be accompanied by screaming and yelling. Fever often occurs.

The head grows more slowly than in healthy children of that age. There is a smaller head circumference and the brain volume is also smaller.
The decline is noticeable in hand use, walking and other motor skills, (also think of dyspraxia, difficulty in controlling body movements (ataxia), including eye movements), speech, cognitive skills and difficulty with communication.

The children can become withdrawn and no longer laugh or play. Epilepsy may also occur.

 

After this decline, a stable phase can follow, which can last a long time. Sometimes some progress can be seen.

NB!
There are many variants of Rett syndrome. As a result, the severity and degree of handicaps may vary. There is, among other things, a milder variant in girls with only mild learning difficulties. However, this is very exceptional.

 

Genetic disorder with metabolic characteristics, mainly in girls

Rett syndrome is a genetic disorder. It is one of the disorders that are the result of abnormalities/changes in the genes or chromosomes, the hereditary material.
In most cases, there is a change in the MECP2 gene (gene mutation) and the disorder is not inherited from the parents. It also occurs that there is a deficiency of the hereditary material of the MECP2 gene.

 

The faulty gene that causes Rett syndrome is on the X chromosome. That is why it occurs almost exclusively in girls. Girls have two X chromosomes and boys have a Y chromosome and an X chromosome.

 

In girls, the faulty gene is on one of the two X chromosomes. The healthy X chromosome then makes the girl viable. In boys, this condition is much rarer. Because a boy has one X and one Y chromosome, they are less viable if the gene is on the X chromosome.

 

However, in Klinefelter syndrome, boys have two X and Y chromosomes. They may get Rett syndrome.

There are also boys who have the error on the MECP2 gene in part of their body cells and not in their other body cells (moccasism), and there are boys who have two copies of this MECP2 gene material per chromosome (MECP-2 duplication syndrome).

They have a developmental delay in which epilepsy often occurs, in which they have frequent infections and show autistic characteristics.

 

Rett syndrome is not a degenerative condition because after deterioration there can also be a stable phase with possible progression.
It can be classified as a metabolic disease because the fat production is different than in healthy people. More cholesterol and other fats are produced.

 

Characteristic

Because there are so many variations, no child will have the entire list of the following characteristics.
The symptoms can vary from person to person and from stage to stage. The symptoms can also improve in the stable phase.

• Too little muscle tone immediately after birth (hypotonia). The children have weak muscles. When lifting the child, you will have to support the child well. The children often cannot lift their heads.
• Over time, excessive muscle tension can develop.
  
• Spasticity / high muscle tension, especially in the legs, which also causes the feet to become forced into a position (pointed feet).
  
• The legs may cross in front.
  
• A child may walk on the toes or balls of the feet.
  
• There is a wide gait when walking, which indicates
  difficulty coordinating movements (ataxia).
• Smaller head circumference, smaller brain volume. This is usually noticeable in the first months of life.
  
• Respiratory disorders including respiratory arrest and pauses (
  obstructive sleep apnea syndrome / OSAS), often alternating with hyperventilation (breathing too fast), hypoventilation (breathing too little). This is partly due to the disturbed function of the brain stem
  which regulates the automatic (autonomous) functions partly because the respiratory tract is blocked. The flaccid muscles of the uvula then sink into the throat. Some researchers suggest that this can lead to sudden cot death (death in sleep) in the first months.
• Sleep problems. The brain stem controls the ability to sleep, but sleep apnea can cause the person to wake up and sleep for a shorter period of time. Snoring is a striking feature of this form of apnea.
  
• Abnormalities in the EEG.
  The brain film often shows abnormalities related to epilepsy, but often a general delay can also be seen. Slow EEG.
  
• Epilepsy in approximately 80% of children with Rett syndrome. This can vary from staring (absences) to a seizure in the entire body.
• ECG abnormalities, ranging from abnormally long pauses between heartbeats or other forms of heart rhythm disorder (arrhythmia).
  
• Development slows down and comes to a standstill.
  
• Loss of the ability to grasp things. Hand use becomes noticeably different. There is repeated hand wringing, clapping and hand waving.
  
• Loss of the ability to speak. Initially, a child may stop saying words. Language development is disrupted. Some children can say a few words. In the milder variant, children can make simple sentences.
  
• Communication comes to a standstill but can improve somewhat later. Communication via pictures is sometimes possible.
  
• The child may start grinding teeth (bruxism).
  
• Anxiety and changes in behavior.
  
• Serious problems with balance or coordination. It can lead to the inability to walk. Although a large proportion of people with Rett can still walk at a later age. Sitting is also no longer possible.
• Growth in height and weight lag behind.
  
• The back and chest can become curved; a sideways curvature of the spine (scoliosis). In some cases, the curvature of the spine can become so severe that it makes breathing difficult, and surgery is necessary.
  Excessive kyphosis (curvature of the spine in the chest area) also occurs regularly. In that case, surgery is sometimes necessary to prevent, among other things, the lungs from being compressed.
  
• The children often have small hands and feet.
  
• There is a greater chance of having reduced bone density in the bones, which makes the bones more likely to break in the event of a fall.
  
• Visually impaired, CVI (cerebral visual impairment: the brain processes visual stimuli differently), strabismus.
  
• Problems with eating. Chewing and swallowing are difficult. Underweight is common. As a result, some people with Rett syndrome are dependent on feeding tubes.
  
• Heartburn (gastroesophageal reflux), the acidic stomach contents come up into the throat and esophagus and that can cause inflammation
  
• Drooling due to the weak muscles of the throat and mouth
  
• Poor physical condition and increased risk of infections
  
• Poor blood circulation in, among other things, hands, legs and feet
  
• Incontinence
  
• Difficult bowel movements / constipation with abdominal complaints.

 

More information

• International Rett Syndrome Foundation

• https://en.wikipedia.org/wiki/Rett_syndrome
• Mayo Clinic